663 research outputs found
Design and testing of a high power spacecraft thermal management system
The design and test results are presented of an ammonia hybrid capillary pumped loop thermal control system which could be used for heat acquisition and transport on future large space platforms and attached payloads, such as those associated with the NASA Space Station. The High Power Spacecraft Thermal Management System (HPSTM) can operate as either a passive, capillary pumped two phase thermal control system, or, when additional pressure head is required, as a mechanically pumped loop. Testing has shown that in the capillary mode, the HPSTM evaporators can acquire a total heat load of between 600 W and 24 kW, transported over 10 meters, at a maximum heat flux density of 4.3 W/sq cm. With the mechanical pump circulating the ammonia, a heat acquisition potential of 52 kW was demonstrated for 15 minutes without an evaporator failure. These results represent a significant improvement over the maximum transport capability previously displayed in other capillary systems. The HPSTM system still retains the proven capillary capabilities of heat load sharing and flow control between evaporator plates, rapid power cycling, and nonuniform heating in both the capillary and hybrid operating modes
Phylogenomic approaches to common problems encountered in the analysis of low copy repeats: The sulfotransferase 1A gene family example
BACKGROUND: Blocks of duplicated genomic DNA sequence longer than 1000 base pairs are known as low copy repeats (LCRs). Identified by their sequence similarity, LCRs are abundant in the human genome, and are interesting because they may represent recent adaptive events, or potential future adaptive opportunities within the human lineage. Sequence analysis tools are needed, however, to decide whether these interpretations are likely, whether a particular set of LCRs represents nearly neutral drift creating junk DNA, or whether the appearance of LCRs reflects assembly error. Here we investigate an LCR family containing the sulfotransferase (SULT) 1A genes involved in drug metabolism, cancer, hormone regulation, and neurotransmitter biology as a first step for defining the problems that those tools must manage. RESULTS: Sequence analysis here identified a fourth sulfotransferase gene, which may be transcriptionally active, located on human chromosome 16. Four regions of genomic sequence containing the four human SULT1A paralogs defined a new LCR family. The stem hominoid SULT1A progenitor locus was identified by comparative genomics involving complete human and rodent genomes, and a draft chimpanzee genome. SULT1A expansion in hominoid genomes was followed by positive selection acting on specific protein sites. This episode of adaptive evolution appears to be responsible for the dopamine sulfonation function of some SULT enzymes. Each of the conclusions that this bioinformatic analysis generated using data that has uncertain reliability (such as that from the chimpanzee genome sequencing project) has been confirmed experimentally or by a "finished" chromosome 16 assembly, both of which were published after the submission of this manuscript. CONCLUSION: SULT1A genes expanded from one to four copies in hominoids during intra-chromosomal LCR duplications, including (apparently) one after the divergence of chimpanzees and humans. Thus, LCRs may provide a means for amplifying genes (and other genetic elements) that are adaptively useful. Being located on and among LCRs, however, could make the human SULT1A genes susceptible to further duplications or deletions resulting in 'genomic diseases' for some individuals. Pharmacogenomic studies of SULT1Asingle nucleotide polymorphisms, therefore, should also consider examining SULT1A copy number variability when searching for genotype-phenotype associations. The latest duplication is, however, only a substantiated hypothesis; an alternative explanation, disfavored by the majority of evidence, is that the duplication is an artifact of incorrect genome assembly
Integrating protein structures and precomputed genealogies in the Magnum database: Examples with cellular retinoid binding proteins
BACKGROUND: When accurate models for the divergent evolution of protein sequences are integrated with complementary biological information, such as folded protein structures, analyses of the combined data often lead to new hypotheses about molecular physiology. This represents an excellent example of how bioinformatics can be used to guide experimental research. However, progress in this direction has been slowed by the lack of a publicly available resource suitable for general use. RESULTS: The precomputed Magnum database offers a solution to this problem for ca. 1,800 full-length protein families with at least one crystal structure. The Magnum deliverables include 1) multiple sequence alignments, 2) mapping of alignment sites to crystal structure sites, 3) phylogenetic trees, 4) inferred ancestral sequences at internal tree nodes, and 5) amino acid replacements along tree branches. Comprehensive evaluations revealed that the automated procedures used to construct Magnum produced accurate models of how proteins divergently evolve, or genealogies, and correctly integrated these with the structural data. To demonstrate Magnum's capabilities, we asked for amino acid replacements requiring three nucleotide substitutions, located at internal protein structure sites, and occurring on short phylogenetic tree branches. In the cellular retinoid binding protein family a site that potentially modulates ligand binding affinity was discovered. Recruitment of cellular retinol binding protein to function as a lens crystallin in the diurnal gecko afforded another opportunity to showcase the predictive value of a browsable database containing branch replacement patterns integrated with protein structures. CONCLUSION: We integrated two areas of protein science, evolution and structure, on a large scale and created a precomputed database, known as Magnum, which is the first freely available resource of its kind. Magnum provides evolutionary and structural bioinformatics resources that are useful for identifying experimentally testable hypotheses about the molecular basis of protein behaviors and functions, as illustrated with the examples from the cellular retinoid binding proteins
Capabilities of Earth-based radar facilities for near-Earth asteroid observations
We evaluated the planetary radar capabilities at Arecibo, the Goldstone 70-m
DSS-14 and 34-m DSS-13 antennas, the 70-m DSS-43 antenna at Canberra, the Green
Bank Telescope, and the Parkes Radio Telescope in terms of their relative
sensitivities and the number of known near-Earth asteroids (NEAs) detectable
per year in monostatic and bistatic configurations. In the 2015 calendar year,
monostatic observations with Arecibo and DSS-14 were capable of detecting 253
and 131 NEAs respectively, with signal-to-noise ratios (SNRs) greater than
30/track. Combined, the two observatories were capable of detecting 276 NEAs.
Of these, Arecibo detected 77 and Goldstone detected 32, or 30% and 24% the
numbers that were possible. The two observatories detected an additional 18 and
7 NEAs respectively, with SNRs of less than 30/track. This indicates that a
substantial number of potential targets are not being observed. The bistatic
configuration with DSS-14 transmitting and the Green Bank Telescope receiving
was capable of detecting about 195 NEAs, or ~50% more than with monostatic
observations at DSS-14. Most of the detectable asteroids were targets of
opportunity that were discovered less than 15 days before the end of their
observing windows. About 50% of the detectable asteroids have absolute
magnitudes > 25, which corresponds diameters < ~30 m.Comment: 12 pages, 7 figures, Accepted to A
Automethylation of G9a and its implication in wider substrate specificity and HP1 binding.
Methylation of lysine residues on histones participates in transcriptional gene regulation. Lysine 9 methylation of histone H3 is a transcriptional repression signal, mediated by a family of SET domain containing AdoMet-dependent enzymes. G9a methyltransferase is a euchromatic histone H3 lysine 9 methyltransferase. Here, G9a is shown to methylate other cellular proteins, apart from histone H3, including automethylation of K239 residue. Automethylation of G9a did not impair or activate the enzymatic activity in vitro. The automethylation motif of G9a flanking target K239 (ARKT) has similarity with histone H3 lysine 9 regions (ARKS), and is identical to amino acids residues in EuHMT (ARKT) and mAM (ARKT). Under steady-state kinetic assay conditions, full-length G9a methylates peptides representing ARKS/T motif of H3, G9a, mAM and EuHMT efficiently. Automethylation of G9a at ARKT motif creates a binding site for HP1 class of protein and mutation of lysine in the motif impairs this binding. In COS-7 cells GFP fusion of the wild-type G9a co-localized with HP1alpha and HP1gamma isoforms whereas the G9a mutant with K239A displayed poor co-localization. Thus, apart from transcriptional repression and regulatory roles of lysine methylation, the non-histone protein methylation may create binding sites for cellular protein-protein interactions
Fast and Reliable Reduced-Order Models for Cardiac Electrophysiology
Mathematical models of the human heart are increasingly playing a vital role
in understanding the working mechanisms of the heart, both under healthy
functioning and during disease. The aim is to aid medical practitioners
diagnose and treat the many ailments affecting the heart. Towards this,
modelling cardiac electrophysiology is crucial as the heart's electrical
activity underlies the contraction mechanism and the resulting pumping action.
The governing equations and the constitutive laws describing the electrical
activity in the heart are coupled, nonlinear, and involve a fast moving wave
front, which is generally solved by the finite element method. The simulation
of this complex system as part of a virtual heart model is challenging due to
the necessity of fine spatial and temporal resolution of the domain. Therefore,
efficient surrogate models are needed to predict the dynamics under varying
parameters and inputs. In this work, we develop an adaptive, projection-based
surrogate model for cardiac electrophysiology. We introduce an a posteriori
error estimator that can accurately and efficiently quantify the accuracy of
the surrogate model. Using the error estimator, we systematically update our
surrogate model through a greedy search of the parameter space. Furthermore,
using the error estimator, the parameter search space is dynamically updated
such that the most relevant samples get chosen at every iteration. The proposed
adaptive surrogate modelling technique is tested on three benchmark models to
illustrate its efficiency, accuracy, and ability of generalization.Comment: 28 pages, 17 figures, 1 tabl
Hillslope Asymmetry Maps Reveal Widespread, Multi-Scale Organization
Hillslope asymmetry is the condition in which oppositely-facing hillslopes within an area have differing average slope angles, and indicates aspect-related variability in hillslope evolution. As such, the presence, orientation and magnitude of asymmetry may be a useful diagnostic for understanding process dominance. We present a new method for quantifying and mapping the spatial distribution of hillslope asymmetry across large areas. Resulting maps for the American Cordillera of the Western Hemisphere and the western United States reveal that hillslope asymmetry is widespread, with distinct trends at continental to drainage scales. Spatial patterns of asymmetry correlate with latitude along the American Cordillera, mountain-range orientation for many ranges in the western United States, and elevation in the Idaho Batholith of the Northern Rocky Mountains. Spatial organization suggests that non-stochastic, process-driven controls cause these patterns. The hillslope asymmetry metric objectively captures previously-documented extents and frequencies of valley asymmetry for the Gabilan Mesa of the central California Coast Range. Broad-scale maps of hillslope asymmetry are of interest to a wide range of disciplines, as spatial patterns may reflect the influence of tectonics, atmospheric circulation, topoclimate, geomorphology, hydrology, soils and ecology on landscape evolution. These maps identify trends and regions of hillslope asymmetry, allow possible drivers to be spatially constrained, and facilitate the extrapolation of site-specific results to broader regions
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